title: Sterol metabolism disorders and neurodevelopment-an update.
abstract: Cholesterol has numerous quintessential functions in normal cell physiology, as well as in embryonic and postnatal development. It is a major component of cell membranes and myelin, and is a precursor of steroid hormones and bile acids. The development of the blood brain barrier likely around 12-18 weeks of human gestation makes the developing embryonic/fetal brain dependent on endogenous cholesterol synthesis. Known enzyme defects along the cholesterol biosynthetic pathway result in a host of neurodevelopmental and behavioral findings along with CNS structural anomalies. In this article, we review sterol synthesis disorders in the pre- and post-squalene pathway highlighting neurodevelopmental aspects that underlie the clinical presentations and course of Smith-Lemli-Opitz Syndrome (SLOS), mevalonic aciduria (MVA) or the milder version hyper-immunoglobulinemia D and periodic fever syndrome (HIDS), Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis (ABS1), congenital hemidysplasia with icthyosiform nevus and limb defects (CHILD) syndrome, CK syndrome, sterol C4 methyl oxidase (SC4MOL) deficiency, X-linked dominant chondrodysplasia punctata 2(CDPX2)/ Conradi Hunermann syndrome, lathosterolosis and desmosterolosis, We also discuss current controversies and share thoughts on future directions in the field.
authors.affiliation: Department of Pediatrics, University of Pittsburgh Medical Center, Pennsylvania, USA.
authors.forename: Shibani
authors.initials: S
authors.lastname: Kanungo
authors.forename: Neelkamal
authors.initials: N
authors.lastname: Soares
authors.forename: Miao
authors.initials: M
authors.lastname: He
authors.forename: Robert D
authors.initials: RD
authors.lastname: Steiner
mesh_terms: D000015:Abnormalities, Multiple / Q000378:metabolism; D000818:Animals; D002784:Cholesterol / Q000172:deficiency; D002806:Chondrodysplasia Punctata / Q000378:metabolism*; D040181:Genetic Diseases, X-Linked / Q000378:metabolism; D006801:Humans; D016113:Ichthyosiform Erythroderma, Congenital / Q000378:metabolism; D017880:Limb Deformities, Congenital / Q000378:metabolism; D008052:Lipid Metabolism, Inborn Errors / Q000378:metabolism; D054078:Mevalonate Kinase Deficiency / Q000201:enzymology / Q000378:metabolism*; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000172:deficiency / Q000378:metabolism; D019082:Smith-Lemli-Opitz Syndrome / Q000201:enzymology / Q000378:metabolism*; D043202:Steroid Metabolism, Inborn Errors / Q000378:metabolism*; D013261:Sterols / Q000378:metabolism*
chemical_list: D013261:Sterols; D002784:Cholesterol; D044925:Oxidoreductases Acting on CH-CH Group Donors